Cardiology News

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

A version of this article first appeared on Medscape.com.

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

A version of the article first appeared on Medscape.com.

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

A version of the article first appeared on Medscape.com.

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

A version of the article first appeared on Medscape.com.

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

A version of this article first appeared on Medscape.com.

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

A version of this article first appeared on Medscape.com.

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

A version of this article first appeared on Medscape.com.

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

A version of this article first appeared on Medscape.com.

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

A version of this article first appeared on Medscape.com.

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

A version of this article first appeared on Medscape.com.

The American Heart Association and the American College of Cardiology have issued a new report on medical ethics and professionalism in cardiovascular medicine.

The report addresses a variety of topics including diversity, equity, inclusion, and belonging; racial, ethnic and gender inequities; conflicts of interest; clinician well-being; data privacy; social justice; and modern health care delivery systems.

The 54-page report is based on the proceedings of the joint 2020 Consensus Conference on Professionalism and Ethics, held Oct. 19 and 20, 2020. It was published online May 11 in Circulation and the Journal of the American College of Cardiology .

The 2020 consensus conference on professionalism and ethics came at a time even more fraught than the eras of the three previous meetings on the same topics, held in 1989, 1997, and 2004, the writing group notes.

“We have seen the COVID-19 pandemic challenge the physical and economic health of the entire country, coupled with a series of national tragedies that have awakened the call for social justice,” conference cochair C. Michael Valentine, MD, said in a news release.

“There is no better time than now to review, evaluate, and take a fresh perspective on medical ethics and professionalism,” said Dr. Valentine, professor of medicine at the Heart and Vascular Center, University of Virginia, Charlottesville.

“We hope this report will provide cardiovascular professionals and health systems with the recommendations and tools they need to address conflicts of interest; racial, ethnic, and gender inequities; and improve diversity, inclusion, and wellness among our workforce,” Dr. Valentine added. “The majority of our members are now employed and must be engaged as the leaders for change in cardiovascular care.”
 

Road map to improve diversity, achieve allyship

The writing committee was made up of a diverse group of cardiologists, internists, and associated health care professionals and laypeople and was organized into five task forces, each addressing a specific topic: conflicts of interest; diversity, equity, inclusion, and belonging; clinician well-being; patient autonomy, privacy, and social justice in health care; and modern health care delivery.

The report serves as a road map to achieve equity, inclusion, and belonging among cardiovascular professionals and calls for ongoing assessment of the professional culture and climate, focused on improving diversity and achieving effective allyship, the writing group says.

The report proposes continuous training to address individual, structural, and systemic racism, sexism, homophobia, classism, and ableism.

It offers recommendations for championing equity in patient care that include an annual review of practice records to look for differences in patient treatment by race, ethnicity, zip code, and primary language.

The report calls for a foundation of training in allyship and antiracism as part of medical school course requirements and experiences: A required course on social justice, race, and racism as part of the first-year curriculum; school programs and professional organizations supporting students, trainees, and members in allyship and antiracism action; and facilitating immersion and partnership with surrounding communities.

“As much as 80% of a person’s health is determined by the social and economic conditions of their environment,” consensus cochair Ivor Benjamin, MD, said in the release.

“To achieve social justice and mitigate health disparities, we must go to the margins and shift our discussions to be inclusive of populations such as rural and marginalized groups from the perspective of health equity lens for all,” said Dr. Benjamin, professor of medicine, Medical College of Wisconsin, Milwaukee.

The report also highlights the need for psychosocial support of the cardiovascular community and recommends that health care organizations prioritize regular assessment of clinicians’ well-being and engagement.

It also recommends addressing the well-being of trainees in postgraduate training programs and calls for an ombudsman program that allows for confidential reporting of mistreatment and access to support.

The report also highlights additional opportunities to:

• improve the efficiency of health information technology, such as electronic health records, and reduce the administrative burden
• identify and assist clinicians who experience mental health conditions, , or 
• emphasize patient autonomy using shared decision-making and patient-centered care that is supportive of the individual patient’s values
• increase privacy protections for patient data used in research
• maintain integrity as new ways of delivering care, such as telemedicine, team-based care approaches, and physician-owned specialty centers emerge
• perform routine audits of electronic health records to promote optimal patient care, as well as ethical medical practice
• expand and make mandatory the reporting of intellectual or associational interests in addition to relationships with industry

The report’s details and recommendations will be presented and discussed Saturday, May 15, at 8:00 AM ET, during ACC.21. The session is titled Diversity and Equity: The Means to Expand Inclusion and Belonging.

The AHA will present a live webinar and six-episode podcast series (available on demand) to highlight the report’s details, dialogue, and actionable steps for cardiovascular and health care professionals, researchers, and educators.

This research had no commercial funding. The list of 40 volunteer committee members and coauthors, including their disclosures, are listed in the original report.

A version of this article first appeared on Medscape.com.

The American Heart Association and the American College of Cardiology have issued a new report on medical ethics and professionalism in cardiovascular medicine.

The report addresses a variety of topics including diversity, equity, inclusion, and belonging; racial, ethnic and gender inequities; conflicts of interest; clinician well-being; data privacy; social justice; and modern health care delivery systems.

The 54-page report is based on the proceedings of the joint 2020 Consensus Conference on Professionalism and Ethics, held Oct. 19 and 20, 2020. It was published online May 11 in Circulation and the Journal of the American College of Cardiology .

The 2020 consensus conference on professionalism and ethics came at a time even more fraught than the eras of the three previous meetings on the same topics, held in 1989, 1997, and 2004, the writing group notes.

“We have seen the COVID-19 pandemic challenge the physical and economic health of the entire country, coupled with a series of national tragedies that have awakened the call for social justice,” conference cochair C. Michael Valentine, MD, said in a news release.

“There is no better time than now to review, evaluate, and take a fresh perspective on medical ethics and professionalism,” said Dr. Valentine, professor of medicine at the Heart and Vascular Center, University of Virginia, Charlottesville.

“We hope this report will provide cardiovascular professionals and health systems with the recommendations and tools they need to address conflicts of interest; racial, ethnic, and gender inequities; and improve diversity, inclusion, and wellness among our workforce,” Dr. Valentine added. “The majority of our members are now employed and must be engaged as the leaders for change in cardiovascular care.”
 

Road map to improve diversity, achieve allyship

The writing committee was made up of a diverse group of cardiologists, internists, and associated health care professionals and laypeople and was organized into five task forces, each addressing a specific topic: conflicts of interest; diversity, equity, inclusion, and belonging; clinician well-being; patient autonomy, privacy, and social justice in health care; and modern health care delivery.

The report serves as a road map to achieve equity, inclusion, and belonging among cardiovascular professionals and calls for ongoing assessment of the professional culture and climate, focused on improving diversity and achieving effective allyship, the writing group says.

The report proposes continuous training to address individual, structural, and systemic racism, sexism, homophobia, classism, and ableism.

It offers recommendations for championing equity in patient care that include an annual review of practice records to look for differences in patient treatment by race, ethnicity, zip code, and primary language.

The report calls for a foundation of training in allyship and antiracism as part of medical school course requirements and experiences: A required course on social justice, race, and racism as part of the first-year curriculum; school programs and professional organizations supporting students, trainees, and members in allyship and antiracism action; and facilitating immersion and partnership with surrounding communities.

“As much as 80% of a person’s health is determined by the social and economic conditions of their environment,” consensus cochair Ivor Benjamin, MD, said in the release.

“To achieve social justice and mitigate health disparities, we must go to the margins and shift our discussions to be inclusive of populations such as rural and marginalized groups from the perspective of health equity lens for all,” said Dr. Benjamin, professor of medicine, Medical College of Wisconsin, Milwaukee.

The report also highlights the need for psychosocial support of the cardiovascular community and recommends that health care organizations prioritize regular assessment of clinicians’ well-being and engagement.

It also recommends addressing the well-being of trainees in postgraduate training programs and calls for an ombudsman program that allows for confidential reporting of mistreatment and access to support.

The report also highlights additional opportunities to:

• improve the efficiency of health information technology, such as electronic health records, and reduce the administrative burden
• identify and assist clinicians who experience mental health conditions, , or 
• emphasize patient autonomy using shared decision-making and patient-centered care that is supportive of the individual patient’s values
• increase privacy protections for patient data used in research
• maintain integrity as new ways of delivering care, such as telemedicine, team-based care approaches, and physician-owned specialty centers emerge
• perform routine audits of electronic health records to promote optimal patient care, as well as ethical medical practice
• expand and make mandatory the reporting of intellectual or associational interests in addition to relationships with industry

The report’s details and recommendations will be presented and discussed Saturday, May 15, at 8:00 AM ET, during ACC.21. The session is titled Diversity and Equity: The Means to Expand Inclusion and Belonging.

The AHA will present a live webinar and six-episode podcast series (available on demand) to highlight the report’s details, dialogue, and actionable steps for cardiovascular and health care professionals, researchers, and educators.

This research had no commercial funding. The list of 40 volunteer committee members and coauthors, including their disclosures, are listed in the original report.

A version of this article first appeared on Medscape.com.

The American Heart Association and the American College of Cardiology have issued a new report on medical ethics and professionalism in cardiovascular medicine.

The report addresses a variety of topics including diversity, equity, inclusion, and belonging; racial, ethnic and gender inequities; conflicts of interest; clinician well-being; data privacy; social justice; and modern health care delivery systems.

The 54-page report is based on the proceedings of the joint 2020 Consensus Conference on Professionalism and Ethics, held Oct. 19 and 20, 2020. It was published online May 11 in Circulation and the Journal of the American College of Cardiology .

The 2020 consensus conference on professionalism and ethics came at a time even more fraught than the eras of the three previous meetings on the same topics, held in 1989, 1997, and 2004, the writing group notes.

“We have seen the COVID-19 pandemic challenge the physical and economic health of the entire country, coupled with a series of national tragedies that have awakened the call for social justice,” conference cochair C. Michael Valentine, MD, said in a news release.

“There is no better time than now to review, evaluate, and take a fresh perspective on medical ethics and professionalism,” said Dr. Valentine, professor of medicine at the Heart and Vascular Center, University of Virginia, Charlottesville.

“We hope this report will provide cardiovascular professionals and health systems with the recommendations and tools they need to address conflicts of interest; racial, ethnic, and gender inequities; and improve diversity, inclusion, and wellness among our workforce,” Dr. Valentine added. “The majority of our members are now employed and must be engaged as the leaders for change in cardiovascular care.”
 

Road map to improve diversity, achieve allyship

The writing committee was made up of a diverse group of cardiologists, internists, and associated health care professionals and laypeople and was organized into five task forces, each addressing a specific topic: conflicts of interest; diversity, equity, inclusion, and belonging; clinician well-being; patient autonomy, privacy, and social justice in health care; and modern health care delivery.

The report serves as a road map to achieve equity, inclusion, and belonging among cardiovascular professionals and calls for ongoing assessment of the professional culture and climate, focused on improving diversity and achieving effective allyship, the writing group says.

The report proposes continuous training to address individual, structural, and systemic racism, sexism, homophobia, classism, and ableism.

It offers recommendations for championing equity in patient care that include an annual review of practice records to look for differences in patient treatment by race, ethnicity, zip code, and primary language.

The report calls for a foundation of training in allyship and antiracism as part of medical school course requirements and experiences: A required course on social justice, race, and racism as part of the first-year curriculum; school programs and professional organizations supporting students, trainees, and members in allyship and antiracism action; and facilitating immersion and partnership with surrounding communities.

“As much as 80% of a person’s health is determined by the social and economic conditions of their environment,” consensus cochair Ivor Benjamin, MD, said in the release.

“To achieve social justice and mitigate health disparities, we must go to the margins and shift our discussions to be inclusive of populations such as rural and marginalized groups from the perspective of health equity lens for all,” said Dr. Benjamin, professor of medicine, Medical College of Wisconsin, Milwaukee.

The report also highlights the need for psychosocial support of the cardiovascular community and recommends that health care organizations prioritize regular assessment of clinicians’ well-being and engagement.

It also recommends addressing the well-being of trainees in postgraduate training programs and calls for an ombudsman program that allows for confidential reporting of mistreatment and access to support.

The report also highlights additional opportunities to:

• improve the efficiency of health information technology, such as electronic health records, and reduce the administrative burden
• identify and assist clinicians who experience mental health conditions, , or 
• emphasize patient autonomy using shared decision-making and patient-centered care that is supportive of the individual patient’s values
• increase privacy protections for patient data used in research
• maintain integrity as new ways of delivering care, such as telemedicine, team-based care approaches, and physician-owned specialty centers emerge
• perform routine audits of electronic health records to promote optimal patient care, as well as ethical medical practice
• expand and make mandatory the reporting of intellectual or associational interests in addition to relationships with industry

The report’s details and recommendations will be presented and discussed Saturday, May 15, at 8:00 AM ET, during ACC.21. The session is titled Diversity and Equity: The Means to Expand Inclusion and Belonging.

The AHA will present a live webinar and six-episode podcast series (available on demand) to highlight the report’s details, dialogue, and actionable steps for cardiovascular and health care professionals, researchers, and educators.

This research had no commercial funding. The list of 40 volunteer committee members and coauthors, including their disclosures, are listed in the original report.

A version of this article first appeared on Medscape.com.

As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19. This guidance was issued on May 13, 2021, and has potentially provided some relief to those who are fully vaccinated, though some are concerned and confused about the implications of this guidance.

This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.

The new guidance indicates that quarantine after a known exposure is no longer necessary.

Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.

The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.¹

Updated guidance for health care facilities

In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.²

There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.

Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.^1,2

Pros and cons to new guidance

Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.

These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.

My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.

There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.

Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
 

How to continue exercising caution

With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.

I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.

There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.

Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.

2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.

As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19. This guidance was issued on May 13, 2021, and has potentially provided some relief to those who are fully vaccinated, though some are concerned and confused about the implications of this guidance.

This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.

The new guidance indicates that quarantine after a known exposure is no longer necessary.

Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.

The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.¹

Updated guidance for health care facilities

In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.²

There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.

Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.^1,2

Pros and cons to new guidance

Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.

These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.

My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.

There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.

Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
 

How to continue exercising caution

With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.

I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.

There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.

Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.

2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.

As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19. This guidance was issued on May 13, 2021, and has potentially provided some relief to those who are fully vaccinated, though some are concerned and confused about the implications of this guidance.

This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.

The new guidance indicates that quarantine after a known exposure is no longer necessary.

Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.

The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.¹

Updated guidance for health care facilities

In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.²

There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.

Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.^1,2

Pros and cons to new guidance

Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.

These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.

My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.

There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.

Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
 

How to continue exercising caution

With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.

I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.

There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.

Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.

2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.